unchanged,161 which has important implications for patients when therapy is discontinued. Agents directed at specifically blocking production or survival of the eosinophil progenitor has the potential to be a long-lasting and XAV-939 site specific therapy. As mentioned above, eosinophil precursors in the bone marrow of non-human primates were reduced following treatment with benralizumab103, indicating that targeting progenitors via cell surface markers is a viable approach to inhibiting eosinophilia. Research focused on further characterizing the biology of the eosinophil progenitor to identify specific surface markers, as well as proliferative and survival signals, may indeed result in new approaches to target eosinophils. Sub-phenotyping Eosinophilic Disorders Post-hoc analyses of data from clinical trials have emphasized the importance of including patients that will likely receive the most therapeutic benefit from a specific agent. For example, in a clinical study in subjects with severe persistent asthma there was an increase in lung function after receiving IL-5-specific antibody therapy in a subgroup of subjects with baseline sputum eosinophil levels greater than 3%102. In subjects with baseline sputum eosinophils less than 3%, there was no difference in change in lung function between those receiving IL-5-specific antibody therapy or placebo, emphasizing the importance of phenotyping patients for baseline eosinophilia to maximize therapeutic benefit. 
It is interesting to note that eosinophilic asthmatic patients are particularly sensitive to the effects of anti-IL-5 and anti-IL-13 when separately used38,83. Elevated levels of serum periostin correlate with eosinophil levels and responsiveness to anti-IL-13, raising the possibility that this subgroup of patients should also be treated with anti-eosinophil therapy, either alone or in combination with anti-IL-13. Blood and tissue eosinophilia can occur in a wide PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19844694 variety of disease processes162 and hypereosinophilic syndrome is a heterogeneous disorder that often has no identifiable cause163. Thus, it is necessary to identify sub-phenotypes of patients with eosinophilic disorders in order to predict treatment responses on the basis of a patient’s genetics or gene expression profiles of affected organs and to tailor therapy for their eosinophil-associated disease accordingly. This approach has proven very effective in patients with hypereosinophilic syndrome, with treatment plans being selected on the basis of the mechanism of eosinophilia, and we believe this should now should be implemented in other more prevalent eosinophilic disorders such as eosinophilic asthma and eosinophilic gastrointestinal disorders. Indeed, whole-genome transcript expression profile analysis has identified a disease-specific tissue transcriptome in the esophagus of patients with eosinophilic esophagitis51,79. The transcriptome analysis has been limited to esophageal biopsies which typically represent mucosa rather than deeper layers of the esophagus. Notably, the transcript is not enriched for eosinophil-specific genes because eosinophils contain relatively low amounts of mRNA compared with other inflammatory and resident cells. Rather, the eosinophilic esophagitis transcriptome provides insight into effector pathways involved in eosinophilic inflammation and can distinguish patients with differing levels of mucosal inflammation as well patients who have been exposed to specific drugs such as topical glucocorticoids16
